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Theses

Le rôle du système nerveux dans la cicatrisation cutanée

Abstract : There are close interactions between the peripheral nervous system (PNS) and the skin. Indeed, the SNP is involved in maintaining the homeostasis of the skin but also in many physiological and pathophysiological processes. Skin wound healing is a complex process which includes various biological processes such as hemostasis, inflammation, re-epithelialization and matrix synthesis. The mechanisms by which the SNP is on the different stages of healing are still rather obscure. We therefore undertook to analyze more precisely the effects of SNP and several neuromediators in the phases of proliferation and remodeling of the healing process. For this, we used as a first step, a model of co-culture between an injured human skin explant and sensory neurons from dorsal root ganglia (DRG) of neonatal rats and analyzed their effects on the proliferation of skin cells and epidermal, on the enzymatic activity of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9), and the balance of expression of collagens type I and III during time of culture. In a second step, we analyzed more precisely the effect of substance P (SP) of Calcitonin-Gene Related Peptide (CGRP) and Vasoactive Intestinal Peptide (VIP) as well as nerve growth factor, Nerve Growth Factor (NGF-β) on the same mechanisms, and added to this study, the effect of these neurotransmitters on the adhesion and differentiation of primary human dermal fibroblasts into myofibroblasts. Thus, this model allowed us to demonstrate that sensory neurons influenced the proliferation of keratinocytes and fibroblasts in promoting it, and they also acted on tissue remodeling by increasing the activity of MMP-2 and - 9 as well as modulating the expression ratio between collagens I and III, in favor of collagen type I. In addition, we show that the studied neuropeptides and NGF-β also promote these mechanisms dose-dependent manner. In addition, neurotransmitters tested promote myofibroblast differentiation of human dermal fibroblasts and increase their ability to adhere to human fibronectin matrix. Using our model can open new fundamental studies but also participate in the development of new molecules promoting healing. We also identified for the first time neuroserpin, an inhibitor of the fibrinolytic system in the skin.
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  • HAL Id : tel-03639129, version 1

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Jérémy Cheret. Le rôle du système nerveux dans la cicatrisation cutanée. Médecine humaine et pathologie. AgroParisTech, 2013. Français. ⟨NNT : 2013AGPT0036⟩. ⟨tel-03639129⟩

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